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It’s time to get serious about the economics of expanded access
By PETER J. PITTS JANUARY 30, 2019



As the winds of change blow away the lingering odors of the “right to try” miasma, it’s time to get serious about expanded access 2.0.

Last week, more than 500 people from industry, academia, government, and patient advocacy groups convened at the National Press Club in Washington to discuss, debate, and develop what comes next for expanded access, also known as compassionate use. The first voice to be heard was Dr. Janet Woodcock, director of the Food and Drug Administration’s Center for Drug Evaluation and Research, in a “fireside chat” I had the honor to moderate. Woodcock shared her belief that expanded access programs are only an iterative step towards more regular and robust use of platform trials.

Platform trials, which involve simultaneously studying multiple therapies for a single disease, provide an innovative pathway for broader access to experimental rare disease treatments. Platform trials can target a variety of subtypes of a disease and enroll “just about anybody who is willing to enter the trial,” Woodcock noted. Her hope is that drug developers will someday be more willing to pursue master protocols (clinical trials intended to simultaneously evaluate more than one investigational drug or more than one cancer type in an overall trial structure) if there were more successful examples of them. Step right up, ladies and gentlemen of the drug development industry.

But the issue of expanded access also exists in the present tense, and many thorny issues persist. One of the most significant issues is the silent elephant in the room: Who should pay for access to experimental medicines, and how much should they pay? Right to try doesn’t mean right to try for free.


Current FDA guidance offers only the ability to recover direct costs such as how much it costs per unit to manufacture the drug — raw materials, labor, and nonreusable supplies and equipment needed to make the quantity of drug required for the patient’s use — or costs to acquire the drug from another manufacturing source plus shipping and handling. In short, drugs offered under an expanded access protocol cannot be priced for profit.

In the wake of the imbroglio over BrainStorm Cell Therapeutics’ considering embracing a right-to-try strategy for expanded access to its experimental ALS compound that included charging a “semi-commercial” price significantly higher than its direct costs, the debate over expanded access reimbursement has come front and center. Insurance doesn’t generally cover treatments that haven’t been approved by regulators. But should it?

In a 1991 memo, Bill Gates said this about the company he co-founded: “Microsoft is not about greed. It’s about innovation and fairness.” How can we apply this philosophy to the economics of expanded access?

Here’s one way to think about that. In his now-classic book, “The Wealth of Nations,” Adam Smith wrote, “It is not from the benevolence of the butcher, the brewer, or the baker that we expect our dinner, but from their regard to their own self-interest.” If we replace those three worthy 18th-century tradesmen with the 21st-century drug developer, payer, and patient, what might the “The Wealth of Expanded Access” look like?

The self-interest of the developer regarding expanded access includes an opportunity for even earlier conversations with formulary committees, an opportunity to recover some development costs, the satisfaction of doing the right thing, and the ability to capture valuable data. Dr. Robert Temple, the deputy center director for clinical science at the FDA’s Center for Drug Evaluation and Research, has said that expanded access protocols can produce data that demonstrate effectiveness in populations outside those studied in registration trials, potentially leading to broader indications.

Where is the self-interest for payers? They must first ask a difficult but crucial question: “Does the experimental treatment have a reasonable chance of a positive clinical impact?” After all, in our increasingly value-based world, should valuable health care resources be used with little hope of success? Within the context of expanded access and timeliness such a query sounds harsh relative to critically ill patients — and the issue of denying hope certainly resonates. So, how can this dilemma be resolved? Should a developer build into its expanded access protocol early-stage payer conversations to “pre-approve” reimbursement? If so, at what levels? Can third-party reimbursement go beyond the FDA-mandated limit of direct costs? This question becomes even more interesting if the expanded use patient is getting the experimental drug for a pre-off-label use, meaning that the approved study design is based on an endpoint for a different condition or conditions. Nobody said this was going to be easy.

Most important, what about the self-interest of the patient and (more broadly speaking) public health? The answer here is clear. For patients, expanded access is all about hope and the possibility of generating valuable evidence so others can benefit from their experiences. It’s here that we find the convergence of self-interest: more positive and predictive clinical outcomes, better data points for value-based reimbursement, and a broader and earlier understanding of benefit/risk ratios.

With all of these opportunities in mind, should we consider that expanded access programs become a “must do” for development programs seeking truncated approval pathways?

FDA Commissioner Scott Gottlieb said recently that drug companies have an “obligation to consider expanded access, especially in areas of unmet medical need.” Should payers be thinking the same thing? It’s time for the discussion about expanded access to get serious and, as Mark Twain reminds us, “The secret of getting ahead is getting started.”

Peter J. Pitts is president of the Center for Medicine in the Public Interest, a visiting professor at the Paris Descartes University Medical School, and a former FDA associate commissioner.

https://www.statnews.com/2019/01/30/get-serious-economics-expanded-access/